# Fibroblast growth factor signaling induces a chondrocyte-like state of peripheral nerve fibroblast during aging

## TL;DR

This study explores how aging affects peripheral nerves and identifies a chondrocyte-like fibroblast state induced by fibroblast growth factor signaling.

## Contribution

The paper reveals a novel mechanism of peripheral nerve aging involving FGF signaling and a chondrocyte-like fibroblast state.

## Key findings

- Phagocytic macrophage numbers increase at the onset of aging in peripheral nerves.
- FGF signaling from adipocytes activates a chondrocyte-like neural fibroblast state during aging.
- FGF2 induces co-expression of SOX9 and FOXC2 in senescent human perineurial fibroblasts, which can be blocked with FGF1.

## Abstract

During aging, peripheral nerves undergo structural and cellular changes that trigger loss of function, impair quality of life, and increase disease risk. During peripheral nerve aging there are cellular and molecular changes, such as increased extracellular matrix deposition. The mechanisms behind these aging-induced alterations remain unclear. Here, we profile mouse sciatic nerves using single nucleus transcriptomics and unravel changes in macrophage subtypes during nerve aging. Phagocytic macrophage numbers increase at the onset of aging, followed by higher numbers of chronic inflammatory macrophages. Based on ligand-receptor analysis, we predict that increased fibroblast growth factor (FGF) signaling from adipocytes activates a chondrocyte-like neural fibroblast state during peripheral nerve aging. Finally, we show that FGF2 induces the co-expression of the chondrocyte markers SOX9 and FOXC2 in senescent human perineurial fibroblast, that can be blocked with FGF1. In conclusion, our findings reveal some of the molecular mechanisms of peripheral nerve aging by FGF-regulated induction of a chondrocyte-like fibroblast state.

Peripheral nerve aging involves structural changes and extracellular matrix deposition. Here, the authors show peripheral nerve cell population shifts and induction of a chondrocyte-like fibroblast state through fibroblast growth factor signaling during aging.